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Neuroendocrinology. 2017;105(4):412-425. doi: 10.1159/000475527. Epub 2017 Aug 12.

Digestive System Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

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Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France.


Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) are a heterogeneous subgroup of rare neoplasms that represent about a third of all poorly differentiated neuroendocrine carcinomas (PDNEC). MiNEN combine a neuroendocrine component, usually a PDNEC, and a non-neuroendocrine component, generally an adenocarcinoma, both accounting for at least 30% of the neoplasm. MiNEN are classified as high-, intermediate-, or low-grade malignancies depending on the metastatic potential of the tumour components. High-grade malignant component should be considered even if it represents <30% of the tumour. The prognosis of MiNEN is generally intermediate between those of the two "pure" components composing it. The aim of this comprehensive review of the literature is to suggest a standardized management of MiNEN. An increasing body of evidence suggests that PDNEC components share molecular abnormalities with their adenocarcinoma counterparts, but also display additional alterations. This advocates for a common origin, and that the presence of a PDNEC component in an adenocarcinoma could indicate a turning point in carcinogenesis.


Adenocarcinoma; Chemotherapy; Epidemiology; Mixed tumours; Neuroendocrine tumours; Prognosis; Treatment

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